Antibodies have high-degree identification abilities with respect to their corresponding antigens, and many cytotoxic drug molecules cannot be used for cancer therapy because they cannot selectively kill cancer cells. Therefore, the connection of antibodies and highly toxic drugs (such as toxins) becomes a highly selective and specific conjugated drug.
An antibody-drug conjugate (ADC) is composed of antibodies, linkers, and drugs (such as toxins). However, these toxins appear to be highly cytotoxic (IC50<1 nM) due to they have to be performed with high dose. One of the toxins commonly used in ADCs is auristatin derivative such as MMAE and MMAF.
One of the linkers commonly used in ADCs is MC-Val-Cit. Among these commonly used linkers, the MC-Val-Cit-PAB developed by Seattle Genetics is the most widely applied system. Toxins of ADCs are liberated by breaking the bonding linkage between linkers and toxins via cathepsin B. However, the linker system is poor aqueous solubility. It requires a high content, 20%, of organic solvent used as a co-solvent to dissolve the linker-toxin during the conjugation process of ADCs, so that the conjugation reaction can be completed in a homogeneous phase.
However, the above-mentioned introducing organic solvent may result in antibody degeneration or antibody aggregation, and further result in yield reduction or product failure of the ADCs. In addition, incomplete removal of organic solvent may potentially be one of the reasons that the final ADC products cannot pass quality control.
Therefore, the development of novel ADC drugs is a challenge in assisting human beings meet anti-cancer medical needs.